Which Disease State

At least four approaches to drug development can be targeted  

Of course/ subsets exist within each of these four approaches. For example/ within each category there can be patients with mild/ moderate/ or severe disease states and symptoms. Although one drug may work well for patients with mild or moderate disease/ that same drug might not be effective for patients with the most severe conditions. 

A Priori Identification of Potential Drug Responders and Nonresponders 

The results of the Human Genome Project will provide breakthroughs in three major areas  

In the past/ the need to include a plan for the codevelopment of a corresponding diagnostic method to indicate whether a drug would be useful was mainly 

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The abihty to iaduce disease states ia animals by manipulation of the diet was estabUshed ia this period. The classical work by Eijkman (5), ia which a heriheri-like condition was iaduced ia chickens fed on poHshed rice, was significant. These findings led to the concept by Hopkins that small amounts of accessory growth factors are necessary for survival and growth. 

Fig. 9. Human disease states in which vitamin D has been impHcated. D3 = vitamin D DHD = la, 25 — dihydroxyvitamin D ...

Toxic Effects on the Blood-Forming Tissues Reduced formation of erythrocytes and other elements of blood is an indication of damage to the bone marrow. Chemical compounds toxic to the bone marrow may cause pancytopenia, in which the levels of all elements of blood are reduced. Ionizing radiation, benzene, lindane, chlordane, arsenic, chloramphenicol, trinitrotoluene, gold salts, and phenylbutazone all induce pancytopenia. If the damage to the bone marrow is so severe that the production of blood elements is totally inhibited, the disease state is termed aplastic anemia. In the occupational environment, high concentrations of benzene can cause aplastic anemia. 

Because of the relative ease with which they can be obtained, plasma proteins have been smdied extensively in both humans and animals. Considerable information is available about the biosynthesis, turnover, strucmre, and functions of the major plasma proteins. Alterations of their amounts and of their metabolism in many disease states have also been investigated. In recent years, many of the genes for plasma proteins have been cloned and their stmcmres determined. 

In the preceding sections we have outlined and evaluated the methods by which NT function may be studied and considered the general pharmacology of the major NTs. This should enable us to consider the possible role of NTs in disease states and drug action. 

Once the malfunction of a particular NT has been established in a disease state, we need to find ways by which its activity can be restored to normal. The approaches used are indicated in Fig. 14.1 and outlined below. It is assumed that no NT crosses the blood-brain barrier and so its activity must be modified indirectly. 

Efficacy results tables, where you want to see which of the therapies treats the underlying disease state better. 

The promise of the isolation and production of therapeutic polypeptides and proteins demands that for treatment of a chronic disease state an oral delivery system be developed which will protect these valuable agents from the hostile gastric environment. Subsequently, the drugs will have to be completely released in the intestine, preferably in a state that will enhance their rapid dissolution and transport across the gut wall minimizing interaction with intestinal proteases. 

Benzhydrylamine Derivatives Attachment of piperazine nitrogen directly to a benzhydryl carbon leads to a pair of compounds which show vasodilator activity, and which should be useful in disease states marked by impaired blood circulation. Reaction of piperonyl chloride (18) with a mixture of piperazine and piperazine dihydrochloride leads to the monoalkylation product (19). (It may be supposed that the mixture of free base and salt equilibrates to the monobasic salt, thus making the second amine less nucleophilic.) Alkylation of 19 by means of benzhydryl chloride then... 

The release characteristics of polyanhydride systems could be used not only to develop clinical treatments, but also to induce chronic disease states as models for studying immune function. Many current models of chronic diseases are based on induction of acute effects, which do not exhibit the same long-term behavior as the disease being modeled. 

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